Bondable microcapsules and surface functionalized fillers

ABSTRACT

A composition comprising microcapsules functionalized with polymerizable functional groups on the surface of said microcapsules wherein the functional groups form covalent bonds with monomers in the continuous phase to enhance the mechanical properties of the composition.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/513,526 filed on Mar. 22, 2017, which is a 371 National Stage Entryof International Application No. PCT/US2015/051931 filed on Sep. 24,2015, which claims the benefit of U.S. Provisional Patent ApplicationNo. 62/055,127 filed on Sep. 25, 2014, the contents of which areincorporated herein by reference in their entirety.

FIELD OF INVENTION

The present application is generally related to compositions, methodsand products useful for composite materials comprising microcapsules.The compositions comprise microcapsules with polymerizable functionalgroups added to monomeric or polymeric continuous phases that enhancethe mechanical properties of the composite. Further, the microcapsulescan be filled with liquid phases that further improve the mechanicalproperties of the composite, or render the composite bioactive forapplications including, but not limited to, promoting remineralizationand imparting antimicrobial activity to the composite.

BACKGROUND OF THE INVENTION

Dental composite materials are utilized in many cases to fill caries andto improve tooth health. At one time, metal-based amalgams, thenporcelain or other ceramic materials were used in a variety of remedialdental procedures. Now, synthetic composites are used as practicalalternatives to these materials for such procedures. A composite is apolymer, otherwise referred to as a resin, which has at least oneadditive. An additive can be anything added to the polymer or resin toimpart a desired property. The composite generally starts out as a pasteor liquid and begins to harden when it is activated, either by adding acatalyst, adding water or another solvent, or photoactivation.Advantageously, synthetic composites provide an aesthetically morenatural appearance versus porcelain or other ceramic materials.

Synthetic composites are typically made from complex mixtures ofmultiple components. Synthetic composites must be completely dissolvablein a fluid vehicle yet remain flowable and viscous; undergo minimalthermal expansion during polymerization; be biocompatible withsurrounding surfaces of tooth enamel and colloidal dentin; and, haveaesthetic similarity to natural dentition in terms of color tone andpolishable texture. Furthermore, the synthetic composite must havesufficient mechanical strength and elasticity to withstand ordinarycompressive occlusive forces, without abnormal wearing and withoutcausing abrasion to dentinal surfaces.

The different varieties of synthetic composites may be approximatelydivided into three main groups of products: synthetic resin-based dentalcomposites, glass-based dental composites, and hybrid dental composites.

A synthetic resin-based dental composite typically comprises severalmonomers combined together. A monomer is a chemical that can be bound aspart of a polymer. The synthetic resin-based dental composite includesother materials, such as silicate glass or processed ceramic thatprovides an essential durability to the composite. These materials mayalso be made from an inorganic material, consisting of a single type ormixed variety of particulate glass, quartz, or fused silica particles.Using differing types of inorganic materials, with differing diametersizes or size mixtures, results in differing material characteristics.

Glass-based dental composites are made from glass particles, such aspowdered fluoroaluminosilicate, dissolved in an aqueous polyalkenoateacid. An acid/base reaction occurs spontaneously, causing precipitationof a metallic polyalkenoate, which subsequently solidifies gradually.The glass particles may be made from silicate, such as silicone dioxideor aluminum silicate, but may also include an intermixture of barium,borosilicate, alumina, aluminum/calcium, sodium fluoride, zirconium, orother inorganic compounds. Some of the earlier glass-based compositeswere formulated to contain primarily a mixture of acrylic acid anditaconic acid comonomers. However, more recently such hybrid productsare modified to include other polymerizable components, such as HEMA orbis-GMA.

Hybrid composites are the third category of synthetic dental composites.Hybrid composites combine glass particles with one or more polymers.Hybrid composites may comprise water-soluble polymers other thanpolyalkenoate, such as hydroxyethyl methacrylate (HEMA) and othercopolymerizing methacrylate-modified polycarboxylic acids, which arecatalyzed by photo activation. Other hybrid composites may be modifiedto include polymerizable tertiary amines, catalyzed by reaction withperoxides.

Synthetic dental composites are increasingly used more often for dentalprocedures, such as restoration and repair. Restoration and repairinclude, for example, fillings, crowns, bridges, dentures, orthodonticappliances, cements, posts and ancillary parts for dental implants toname a few. Most common, synthetic dental composites are used foranterior Class III and Class V reconstructions, for smaller size Class Iand Class II molar reconstructions, for color-matching of cosmeticveneers, and for cementing of crowns and overlays. Nonetheless certaindisadvantages of these materials have been noted. For example, the traceamounts of unconverted monomers and/or catalyst that may remain withinthe composite and, if subsequently absorbed systemically in humans, maybe potentially physiologically harmful.

Another major drawback associated with synthetic composites is that theytend to wear more rapidly, especially when placed in appositionalcontact with load-bearing dental surfaces, a deficiency that oftenlimits the purposeful use of such materials primarily to repair ofdefects within anterior maxillary or readily visible mandibularsurfaces.

Perhaps the most significant disadvantage associated with syntheticcomposites is that they have a comparatively lower resistance tofracture. Even relatively minor surface discontinuities within thecomposite, whether occurring from injurious trauma or occlusive stress,may progressively widen and expand, eventually resulting in partial orcomplete disintegration of the reconstruction or repair. This greatersusceptibility to fracture is thought to be correlated with the dentalreconstruction or repair.

Fracture susceptibility is also correlated with the proportional volumeof the amount of synthetic composite required, or the lesser fraction ofintact enamel and dentinal tooth material that remains available, priorto reconstruction or repair. It is well established from studies of the“cracked tooth syndrome” that once a damaging fracture has occurred,tooth loss may be almost inevitable, especially for carious teeth thathave been previously filled. An improved synthetic composite havinggreater resistance to fracture would be significantly advantageous.

The susceptibility of fracture and damage to bone tissue is relevant tochildren and adults alike whom require filling of caries in toothmaterials. However, it is known that certain changes in bone mass occurover the life span of an individual. After about the age of 40 andcontinuing to the last stages of life, slow bone loss occurs in both menand women. Loss of bone mineral content can be caused by a variety ofconditions and may result in significant medical problems. If theprocess of tissue mineralization is not properly regulated, the resultcan be too little of the mineral or too much—either of which cancompromise bone health, hardness and strength. A number of bone growthdisorders are known which cause an imbalance in the bone remodelingcycle. Chief among these are metabolic bone diseases such asosteoporosis, osteoplasia (osteomalacia), chronic renal failure andhyperparathyroidism, which result in abnormal or excessive loss of bonemass known as osteopenia. Other bone diseases, such as Paget's disease,also cause excessive loss of bone mass at localized sites.

Osteoporosis is a structural deterioration of the skeleton caused byloss of bone mass resulting from an imbalance in bone formation, boneresorption, or both. Bone resorption is the process by which osteoclastsbreak down bone and release the minerals, resulting in a transfer ofcalcium from bone fluid to the blood. Bone resorption dominates the boneformation phase, thereby reducing the weight-bearing capacity of theaffected bone. In a healthy adult, the rate at which bone is formed andresorbed is tightly coordinated so as to maintain the renewal ofskeletal bone. However, in osteoporotic individuals, an imbalance inthese bone remodeling cycles develops which results in both loss of bonemass and in formation of microarchitectural defects in the continuity ofthe skeleton. These skeletal defects, created by perturbation in theremodeling sequence, accumulate and finally reach a point at which thestructural integrity of the skeleton is severely compromised and bonefracture is likely. Although this imbalance occurs gradually in mostindividuals as they age, it is much more severe and occurs at a rapidrate in postmenopausal women. In addition, osteoporosis also may resultfrom nutritional and endocrine imbalances, hereditary disorders and anumber of malignant transformations.

Osteoporosis in humans is preceded by clinical osteopenia (bone mineraldensity that is greater than one standard deviation but less than 2.5standard deviations below the mean value for young adult bone), acondition found in approximately 25 million people in the United States.Another 7-8 million patients in the United States have been diagnosedwith clinical osteoporosis (defined as bone mineral content greater than2.5 standard deviations below that of mature young adult bone).Osteoporosis is one of the most expensive diseases for the health caresystem, costing billions of dollars annually in the United States. Inaddition to health care related costs, long-term residential care andlost working days add to the financial and social costs of this disease.Worldwide, approximately 75 million people are at risk for osteoporosis.

The frequency of osteoporosis in the human population increases withage, and among Caucasians is predominant in women, who compriseapproximately 80% of the osteoporosis patient pool in the United States.In addition in women, another phase of bone loss occurs possibly due topostmenopausal estrogen deficiencies. During this phase of bone loss,women can lose an additional 10% in the cortical bone and 25% from thetrabecular compartment. The increased fragility and susceptibility tofracture of skeletal bone in the aged is aggravated by the greater riskof accidental falls in this population. More than 1.5 millionosteoporosis-related bone fractures are reported in the United Stateseach year. Fractured hips, wrists, and vertebrae are among the mostcommon injuries associated with osteoporosis. Hip fractures inparticular are extremely uncomfortable and expensive for the patient,and for women correlate with high rates of mortality and morbidity.

Patients suffering from chronic renal (kidney) failure almostuniversally suffer loss of skeletal bone mass, termed renalosteodystrophy. While it is known that kidney malfunction causes acalcium and phosphate imbalance in the blood, to date replenishment ofcalcium and phosphate by dialysis does not significantly inhibitosteodystrophy in patients suffering from chronic renal failure. Inadults, osteodystrophic symptoms often are a significant cause ofmorbidity. In children, renal failure often results in a failure togrow, due to the failure to maintain and/or to increase bone mass.

Osteoplasia, also known as osteomalacia (“soft bones”), is a defect inbone mineralization (e.g., incomplete mineralization), and classicallyis related to vitamin D deficiency (1,25-dihydroxy vitamin D₃). Thedefect can cause compression fractures in bone, and a decrease in bonemass, as well as extended zones of hypertrophy and proliferativecartilage in place of bone tissue. The deficiency may result from anutritional deficiency (e.g., rickets in children), malabsorption ofvitamin D or calcium, and/or impaired metabolism of the vitamin.

Hyperparathyroidism (overproduction of the parathyroid hormone) is knownto cause malabsorption of calcium, leading to abnormal bone loss. Inchildren, hyperparathyroidism can inhibit growth, in adults the skeletonintegrity is compromised and fracture of the ribs and vertebrae arecharacteristic. The parathyroid hormone imbalance typically may resultfrom thyroid adenomas or gland hyperplasia or may result from prolongedpharmacological use of a steroid. Secondary hyperparathyroidism also mayresult from renal osteodystrophy. In the early stages of the disease,osteoclasts are stimulated to resorb bone in response to the excesshormone present. As the disease progresses, the trabecular boneultimately is resorbed and marrow is replaced with fibrosis, macrophagesand areas of hemorrhage as a consequence of microfractures, a conditionis referred to clinically as osteitis fibrosa.

Paget's disease (osteitis deformans) is a disorder currently thought tohave a viral etiology and is characterized by excessive bone resorptionat localized sites which flare and heal but which ultimately are chronicand progressive and may lead to malignant transformation. The diseasetypically affects adults over the age of 25.

Although osteoporosis has been defined as an increase in the risk offracture due to decreased bone mass, none of the presently availabletreatments for skeletal disorders can substantially increase the bonedensity of adults. A strong perception exists among physicians thatdrugs are needed which could increase bone density in adults,particularly in the bones of the wrist, spinal column and hip that areat risk in osteopenia and osteoporosis.

Current strategies for the prevention of osteoporosis may offer somebenefit to individuals but cannot ensure resolution of the disease.These strategies include moderating physical activity, particularly inweight-bearing activities, with the onset of advanced age, includingadequate calcium in the diet, and avoiding consumption of productscontaining alcohol or tobacco. For patients presenting with clinicalosteopenia or osteoporosis, all current therapeutic drugs and strategiesare directed to reducing further loss of bone mass by inhibiting theprocess of bone absorption, a natural component of the bone remodelingprocess that occurs constitutively.

For example, estrogen is now being prescribed to retard bone loss. Thereis, however, some controversy over whether there is any long termbenefit to patients and whether there is any effect at all on patientsover 75 years old. Moreover, use of estrogen is believed to increase therisk of breast and endometrial cancer. High doses of dietary calciumwith or without vitamin D have also been suggested for postmenopausalwomen. However, ingestion of high doses of calcium can often haveunpleasant gastrointestinal side effects, and serum and urinary calciumlevels must be continuously monitored.

Other therapeutics which have been suggested include calcitonin,bisphosphonates, anabolic steroids and sodium fluoride. Suchtherapeutics, however, have undesirable side effects, for example,calcitonin and steroids may cause nausea and provoke an immune reaction,bisphosphonates and sodium fluoride may inhibit repair of fractures,even though bone density increases modestly, which that may preventtheir usage.

The above disorders are examples of conditions that may lead to bonefractures, fissures or splintering of the bones in the individuals whosuffer from a given disorder. Current therapeutic methods areinsufficient to treat the disorders leaving a need for improvedtreatments of bone fractures when they occur in the individual. Thepresent invention provides improved compositions, products and methodsfor locally treating bone fractures, fissures, splintering and similarbreakages of the bone, or by strengthening decomposed bone tissue byincreasing the mechanism of mineralization of the bone. It isconceivable that the current invention also causes mineralization of thesurrounding connective tissue, such as collagen, cartilage, tendons,ligaments and other dense connective tissue and reticular fibers.

The Oral Cavity

With respect to tissue decomposition in the oral cavity, it is commonlyknown in the dental art that certain kinds of tooth decomposition anddecay that occurs over time in the mouth is initiated by acid etching ofthe tooth enamel with the source of the acid being a metaboliteresulting from bacterial and enzymatic action on food particles in theoral cavity. It is generally understood that plaque, a soft accumulationon the tooth surface consisting of an organized structure ofmicroorganisms, proteinaceous and carbohydrate substances, epithelialcells, and food debris, is a contributory factor in the development ofvarious pathological conditions of the teeth and soft tissue of the oralcavity. The saccharolytic organisms of the oral cavity which areassociated with the plaque, cause a demineralization or decalcificationof the tooth beneath the plaque matrix through metabolic activity whichresults in the accumulation and localized concentration of organicacids. The etching and demineralization of the enamel may continue untilthey cause the formation of dental caries and periodontal disease withinthe oral cavity.

Teeth are cycled through periods of mineral loss and repair also as aresult of pH fluctuations in the oral cavity. The overall loss or gainof mineral at a given tooth location determine whether the cariousprocess will regress, stabilize or advance to an irreversible state.Numerous interrelated patient factors affect the balance between theremineralization and demineralization portions of this cycle and includeoral hygiene, diet, and the quantity and quality of saliva. At the mostextreme point in this process, a restoration will be required to repairthe tooth.

Methods for the prevention and reduction of plaque and tooth decaywithin the oral cavity commonly involve the brushing of the teeth usingtoothpastes; mechanical removal of the plaque with dental floss;administration and rinsing of the oral cavity with mouthwashes,dentifrices, and antiseptics; remineralization and whitening of theteeth with fluoride agents, calcium agents and whitening agents, andvarious other applications to the oral cavity. Still missing in thefield is a delivery system for the remineralization of teeth that wouldaddress the challenges of demineralization facing the teeth continuallyin the oral cavity.

A tooth that has reached an advanced stage of decay often requiresinstallation of a dental restoration within the mouth. Half of alldental restorations fail within 10 years and replacing them consumes 60%of the average dentist's practice time. Current dental materials arechallenged by the harsh mechanical and chemical environment of the oralcavity with secondary decay being the major cause of failure.Development of stronger and longer-lasting biocompatible dentalrestorations by engineering novel dental materials or new resin systems,enhancing existing materials, and incorporating bioactive agents inmaterials to combat microbial destruction and to sustain the harshmechanical and chemical environment of the oral cavity continues to bedesired.

Despite numerous preventive oral health strategies, dental cariesremains a significant oral health problem. More than 50% of childrenaged 6-8 will have dental caries and over 80% of adolescents over age 17will have experienced the disease. Caries is also seen in adults both asa primary disease and as recurrent disease in already treated teeth.Advances in diagnosis and treatment have led to noninvasiveremineralizing techniques to treat caries. However mechanical removal ofdiseased hard tissue and restoration and replacement of enamel anddentin is still the most widely employed clinical strategy for treatingprimary caries, restoring function to the tooth and also blockingfurther decay. In addition, nearly 50% of newly placed restorations arereplacement of failed restorations. Clearly, restorative materials are akey component of treating this widespread disease.

The selection of a restorative material has significantly changed inrecent years. While dental amalgam is still considered a cost effectivematerial, there is a growing demand for tooth colored alternatives thatwill provide the same clinical longevity that is enjoyed by dentalamalgam. The use of composite resins has grown significantlyinternationally as a material of choice for replacing amalgam as arestorative material for posterior restorations. This demand ispartially consumer driven by preference for esthetic materials and theconcerns regarding the mercury content of amalgam. It is also driven bydentists recognizing the promise of resin-based bonded materials inpreserving and even supporting tooth structure. Numerous studies havesuggested that bonding the restoration to the remaining tooth structuredecreases fracture of multisurface permanent molar preparations.Unfortunately, posterior teeth restored with direct resin restorativematerials have a higher incidence of secondary caries. This has led toshorter clinical service and narrower clinical indications for compositeresin materials compared to amalgam.

The most frequently cited reason for restoration replacement isrecurrent decay around or adjacent to an existing restoration. It islikely that fracture at the margin due to polymerization shrinkage canlead to a clinical environment at the interface between a restorationand the tooth that collects dental plaque and thus promotes decay.Therefore, developing dental materials with anticaries capability is avery high priority for extending the longevity of restorations.

Tooth Remineralization

Although natural remineralization is always taking place in the oralcavity, the level of activity varies according to conditions in themouth as discussed. Incorporation of fluoride during theremineralization process has been a keystone for caries prevention. Theeffectiveness of fluoride release from various delivery platforms,including certain dental restorative materials has been widelydemonstrated. It is commonly accepted that caries prevention fromfluoride is derived from its incorporation as fluorapatite or fluorideenriched hydroxyapatite in the tooth mineral thereby decreasing thesolubility of tooth enamel. More recently, anticaries activity has beendemonstrated using the strategy of increasing solution calcium andphosphate concentrations to levels that exceed the ambient concentrationin oral fluids. In order for fluoride to be effective at remineralizingpreviously demineralized enamel, a sufficient amount of calcium andphosphate ions must be available. For every two (2) fluoride ions, ten(10) calcium ions and six (6) phosphate ions are required to form a cellof fluorapatite (Ca₁₀(PO₄)₆F₂). Thus the limiting factor for net enamelremineralization is the availability of calcium and fluoride in saliva.

The low solubility of calcium phosphates has limited their use inclinical delivery platforms, especially when in the presence of fluorideions. These insoluble phosphates can only produce available ions fordiffusion into the enamel in an acidic environment. They do noteffectively localize to the tooth surface and are difficult to apply inclinically usable forms. Because of their intrinsic solubility, solublecalcium and phosphate ions can only be used at very low concentrations.Thus they do not produce concentration gradients that drive diffusioninto the subsurface enamel of the tooth. The solubility challenge isexacerbated by the even lower solubility of calcium fluoride phosphates.

Several commercially available approaches exist using calcium andphosphate preparations that have been commercialized into various dentaldelivery models. These have been reportedly compounded to overcome thelimited bioavailability of calcium and phosphate ions for theremineralization process. The first technology uses caseinphosphopeptide (CCP) stabilized with amorphous calcium phosphate (ACP)(RECALDENT® CCP-ACP of Cadbury Enterprises Pte. Ltd.). It ishypothesized that the casein phosphopeptide can facilitate thestabilization of high concentrations of ionically available calcium andphosphate even in the presence of fluoride. This formulation binds topellicle and plaque and while the casein phosphopeptide prevents theformation of dental calculus, the ions are available to diffuse down theconcentration gradient to subsurface enamel lesions facilitatingremineralization. As compared to the CCP-ACP, in the composition of theinvention, biologically available ions are available due to the factthat the salts are already solvated in the microcapsule of theinvention. Amorphous calcium phosphate is not soluble in water orsaliva. Although the manufacturer claims release of bioavailable ionsfrom amorphous calcium phosphate, it is not as a result of thedissolution of the complex. A second technology (ENAMELON®) usesunstabilized amorphous calcium phosphate. Calcium ions and phosphateions are introduced as a dentifrice separately in a dual chamber deviceforming amorphous calcium phosphate in-situ. It is proposed thatformation of the amorphous complex promotes remineralization. A thirdapproach uses a so-called bioactive glass (NOVAMIN® of NovaMinTechnology Inc.) containing calcium sodium phosphosilicate. It isproposed that the glass releases calcium and phosphate ions that areavailable to promote remineralization. More recently dental compositeformulations have been compounded using zirconia-hybridized ACP that mayhave the potential for facilitating clinical remineralization.

While the Recaldent® and Enamelon® preparations have both in-situ andin-vivo evidence suggesting enhanced remineralization, these aretopically applied and do not specifically target the most at risklocation for recurrent caries at the tooth restoration interface. Whilethe bioactive glass and the zirconia-hybridized-ACP filler technologieshave potential, they are relatively inflexible in terms of the range offormulations in which they might be used due to the challenges ofdealing with brittle fillers and some of the limitations on controllingfiller particle size.

Another approach taken to decrease caries in the oral cavity is thelimiting of demineralization of enamel and bone by drinking waterfluoridation. It has been shown that the fluoride contained in drinkingwater incorporates to some extent into hydroxyapatite, the majorinorganic component of enamel and bone. Fluoridated hydroxyapatite isless susceptible to demineralization by acids and is thus seen to resistthe degradation forces of acidic plaque and pocket metabolites. Inaddition, fluoride ion concentration in saliva is increased throughconsumption of fluoridated drinking water. Saliva thus serves as anadditional fluoride ion reservoir and in combination with bufferingsalts naturally found in salivary fluid, fluoride ions are activelyexchanged on the enamel surface, further offsetting the effects ofdemineralizing acid metabolites.

Notwithstanding the established benefits of fluoride treatment of teeth,fluoride ion treatment can result in irregular spotting or blotching ofthe teeth depending on the individual, whether administered throughdrinking water or by topically applied fluoride treatment. This effectis known to be both concentration-related and patient specific. Inaddition, the toxicology of fluoride is being studied as to its longterm effect on human health. Desired is a targeted approach offluoridation in the oral cavity.

Another approach to limiting the proliferation of microflora in the oralenvironment is through topical or systematic application ofbroad-spectrum antibacterial compounds. Reducing the number of oralmicroflorae in the mouth results in a direct reduction or elimination ofplaque and pocket accumulation together with their damaging acidicmetabolite production. The major drawback to this particular approach isthat a wide variety of benign or beneficial strains of bacteria arefound in the oral environment which may be killed by the sameantibacterial compounds in the same manner as the harmful strains. Inaddition, treatment with antibacterial compounds may select for certainbacterial and fungi, which may then become resistant to theantibacterial compound administered and thus proliferate, unrestrainedby the symbiotic forces of a properly balanced microflora population.Thus the application or administration of broad-spectrum antibioticsalone is ill-advised for the treatment of caries and a more specific,targeted approach is desired.

Tooth Whitening

Cosmetic dental whitening or bleaching has become extremely desirable tothe general public. Many individuals desire a “bright” smile and whiteteeth and consider dull and stained teeth cosmetically unattractive.Unfortunately, without preventive or remedial measures, stained teethare almost inevitable due to the absorbent nature of dental material.Everyday activities such as eating, chewing, or drinking certain foodsand beverages (in particular coffee, tea, and red wine) and smoking orother oral use of tobacco products cause undesirable staining ofsurfaces of teeth. Extrinsic staining of the acquired pellicle arises asa result of compounds such as tannins and polyphenolic compounds whichbecome trapped in and tightly bound to the proteinaceous layer on thesurfaces of teeth. This type of staining can usually be removed bymechanical methods of tooth cleaning. In contrast, intrinsic stainingoccurs when staining compounds penetrate the enamel and even the dentinor arise from sources within the tooth. The chromogens or color causingsubstances in these materials become part of the pellicle layer and canpermeate the enamel layer. Even with regular brushing and flossing,years of chromogen accumulation can impart noticeable toothdiscoloration. Intrinsic staining can also result from microbialactivity, including that associated with dental plaque. This type ofstaining is not amenable to mechanical methods of tooth cleaning andchemical methods are required.

Without specifically defining the mechanism of action of the presentinvention, the compositions, products and methods of the presentinvention enable the precipitation of salts onto the surfaces of theteeth in the oral cavity and make the salts available for adherence tothe tooth surface and remineralization of the teeth. The mineralizingsalts are deposited in the interstitial spaces of the teeth, making theteeth smoother, increasing the reflection of light from the surface ofthe teeth and thereby giving the teeth a brighter, more lustrousappearance and whiter visual effect. Furthermore, the remineralizationprocess provides for improved enamel remineralization thus treating andpreventing caries in the oral cavity.

Accordingly, there is need for improved compositions, methods andproducts that overcome the limitations of the prior art. The challengeremains to create microcapsules and microcapsule formulations thatenhance the mechanical properties of the composite and wherein theliquid phases within the semipermeable microcapsules provide beneficialmaterials to the composite or surface to which the composite isattached. Such material, therefore, include materials for use in a toothremineralization technology platform for incorporating stable andeffective tissue remineralization ions that can be incorporated into amyriad of dental materials and variety of products. Such a deliveryplatform would facilitate the formulation of dental products such as anynumber of dentifrices capable of remineralization of the teeth.

The embodiments of the compositions, products and methods, as describedherein, satisfy these and other needs. For purposes of use with a toothmaterial, the ultimate impact is an improved microcapsule having areduction in recurrent caries, the most prevalent reason for restorationreplacement; whitening of the teeth; and resulting improvement inoverall strength and health of the teeth in the oral cavity.

SUMMARY OF THE INVENTION

Compositions, methods, and products that benefit from improvedmechanical properties related to better homogenization of the continuousand discontinuous phase of a composite, by functionalizing the surfaceof a microcapsule which can then covalently bond with other structures.

Another aspect of the present invention provides compositions, productsand methods that use microcapsules comprising a polymerizable functionalgroup therein to enhance the material properties of the composite,wherein the microcapsules can be filled with any number of biologic,mechanical, restorative, or other materials which are suitable fortreating the materials which the composite is attached to. For example,remineralization materials may include salt ions, which serve toincrease bone mineralization at localized sites or remineralization ofteeth directly in the oral cavity. Such materials, thus, may be utilizedin conjunction with treatments of a wide variety of conditions where itis desired to increase bone or tissue mass as a result of any conditionwhich can be improved by bioavailability of physiological salts,particularly of calcium and phosphate.

Another aspect of this invention relates to further improvement ofmechanical properties of a composite by the ability to create novelfillers with unique morphologies and chemical compositions. Accordingly,embodiments as described herein relate to the simplification of amanufacturing process that eliminates the need for additional steps forthe surface treatment of fillers. Accordingly, the embodiments providefor improvements of the mechanical properties of the composite and itdoes so in a way that the filler can be made to carry therapeutic agentsthat can be released in a controllable manner.

In further embodiments, disclosed are compositions and methods thatimprove the mechanical properties of a composite or improve themanufacturing process of fillers used in composites by use ofnontherapeutic fillers. The present invention provides products that areuseful in a number of industries, especially for oral health care. Thepresent invention provides compositions that include fillers disposed ofwithin the discontinuous phase, wherein a particular filler includesliquid filled microcapsules that are surface functionalized with apolymerizable functional group. These fillers, when combined withmonomers and an initiator allow for the generation of a composite thathas the continuous and discontinuous phases covalently bonded together.The covalent bonding of the continuous and discontinuous phases leads toa significant improvement in mechanical properties of a composite,especially in the area of fracture mechanics. The composition of thisinvention affords for the opportunity of producing bondable bioactivemicrocapsules where the microcapsule is filled with a liquid thatcontains a therapeutic agent. The composition of this invention not onlyprovides superior fracture properties by nature of the covalent bondingbetween the filler and continuous phase, but it can provide forimprovement of other mechanical properties if the microcapsule is filledwith energy absorbing materials such as rubbers or silicones.

Another aspect of the disclosure includes bondable bioactivemicrocapsules suitable for industrial products in the dental materialsindustry, wherein liquid encapsulated in the bondable microcapsulecontained aqueous salt solutions of a calcium, phosphate or fluoridecontaining salt, then incorporation of those microcapsules in a dentalmaterials product for promoting remineralization. Furthermore, theliquid encapsulated in the bondable microcapsule contained aqueoussolutions of an antimicrobial agent, including, but not limited tobenzalkonium chloride or cetylpyridinium chloride then incorporation ofthose microcapsules into a dental materials product with antimicrobialproperties would be achieved. Similarly, combinations of remineralizingand antimicrobial compounds are desirable in certain embodiments.

In essence, this invention simultaneously enhances the mechanicalproperties and simplifies the manufacturing of a composite by virtue ofhaving built-in surface functionalization, while adding the benefit ofhaving the filler be therapeutic or mechanically toughening depending onits chemical composition.

Another aspect of the disclosure includes a composition comprising of amonomer, an initiator, and a microcapsule encapsulating an aqueoussolution of a salt, wherein said microcapsule has a surfacefunctionalized with a polymerizable functional group capable ofpolymerizing with said monomer.

Another aspect of the disclosure includes a composition comprising of amonomer, an initiator, and a microcapsule encapsulating an aqueoussolution of a salt, specifically calcium, fluoride or phosphate orcombinations thereof, wherein said microcapsule has a surfacefunctionalized with a polymerizable functional group capable ofpolymerizing with said monomer.

Another aspect of the disclosure includes a composition comprising of apolymeric continuous phase and a microcapsule encapsulating an aqueoussolution of a salt, specifically calcium, fluoride or phosphate orcombinations thereof, wherein said microcapsule has a surfacefunctionalized with a polymerizable functional group capable ofpolymerizing with said monomer.

Another aspect of the disclosure includes a composition comprising of apolymeric continuous phase and a microcapsule encapsulating a fluid,wherein said microcapsule has a surface functionalized with apolymerizable functional group that is covalently bonded to thecontinuous phase.

A further embodiment is directed to a composition comprising acontinuous phase comprising a monomer, and a discontinuous phasecomprising at least one filler comprising a microcapsule encapsulating afluid, and an initiator, wherein said microcapsule has a surfacefunctionalized with a polymerizable functional group capable ofpolymerizing with said monomer.

A further embodiment is directed to a composition comprising of amonomer, an initiator, and a microcapsule encapsulating an aqueoussolution of a salt selected from the group consisting of: benzalkonium,cetylpyridinium, and iodide, and combinations thereof, wherein saidmicrocapsule has a surface functionalized with a polymerizablefunctional group capable of polymerizing with said monomer.

A further embodiment is directed to a composition comprising of a TEGMAand bis-GMA monomers, an initiator, and a microcapsule encapsulating anaqueous solution of a salt selected from the group consisting of:benzalkonium, cetylpyridinium, and iodide, and combinations thereof,wherein said microcapsule has a surface functionalized with apolymerizable functional group capable of polymerizing with saidmonomer. The microcapsule is between 2% and 5% w/w of the compositionand has methacrylate functional groups on the surface, wherein themethacrylate group reacts with the methacrylate groups of the monomersin the continuous phase.

Another aspect of the disclosure provides a method for manufacturing acomposition having a microcapsule and a continuous phase, wherein saidmicrocapsule comprises a functionalized surface capable of covalentlybonding to the continuous phase comprising: mixing an oligomericurethane by reaction of a diol and diisocyanate, in which thediisocyanate is used in molar excess, and reacting for a about 1 hour;adding 2-hydroxyethylmethacrylate to the resulting oligomeric urethanemixture to terminate chain ends with methacrylate functional groups;isolating the functionalized urethane; adding the isolatedfunctionalized urethane to an oil phase comprising an emulsifying agentand an organic solvent wherein a surfactant free inverse emulsion isformed with the addition of an aqueous phase that may contain a salt;adding diol to the surfactant free reverse emulsion to polymerize theurethane oligomers and encapsulate the aqueous solution; and isolatingthe microcapsules by centrifugation.

Another aspect of the disclosure provides a method for manufacturing acomposition having a microcapsule and a continuous phase, wherein saidmicrocapsule comprises a functionalized surface capable of covalentlybonding to the continuous phase comprising: synthesizing oligomeric orpolymeric material with functional groups capable of reacting withmonomers of a continuous phase; isolating the functionalized oligomericor polymeric material; adding the isolated functionalized material to anoil phase comprising an emulsifying agent and an organic solvent whereina surfactant free inverse emulsion is formed with the addition of anaqueous phase that may contain a salt; adding chain extender to thesurfactant free reverse emulsion to increase the molecular weight of thefunctionalized oligomeric or polymeric material and encapsulate theaqueous solution; and isolating the functionalized microcapsules bycentrifugation.

Another aspect of the invention is a method of use any one of thecompositions to impart additional structural features into a polymer orcomposite material.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a drawing of a flowchart showing the preparation of anembodiment of a surface functionalized microcapsule.

FIG. 2 depicts a liquid filled microcapsule having a polymer exteriorand a liquid center, which is in contact with the polymer and attached afunctional group.

FIG. 3 depicts a liquid filled microcapsule and ions disposed oftherein.

FIG. 4 depicts a bondable microcapsule positioned in a mixture ofmonomers, wherein two different monomers are depicted.

FIG. 5 depicts a bondable microcapsule wherein the functional groupattached to the microcapsule is covalently bonded to a polymer.

FIG. 6 depicts two microcapsules bonded to a now polymerized group ofmonomers.

FIG. 7 depicts two possible urethane microcapsules having differentfunctional groups that can react with HEMA to form several differentfunctional microcapsules.

FIG. 8 depicts the methacrylate terminated polyurethane from FIG. 7 anda monomer which are then covalently bonded in the bottom structure.

DETAILED DESCRIPTION OF THE INVENTION

The embodiments of the invention and the various features and advantagesthereto are more fully explained with references to the nonlimitingembodiments and examples that are described and set forth in thefollowing descriptions of those examples. Descriptions of well-knowncomponents and techniques may be omitted to avoid obscuring theinvention. The examples used herein are intended merely to facilitate anunderstanding of ways in which the invention may be practiced and tofurther enable those skilled in the art to practice the invention.Accordingly, the examples and embodiments set forth herein should not beconstrued as limiting the scope of the invention, which is defined bythe claims.

As used herein, terms such as “a,” “an,” and “the” include singular andplural referents unless the context clearly demands otherwise.

As used herein, the term “about” means within 10% of a stated number.

There exists a broad need for improved microcapsule compositions andmethods useful for therapeutic agent delivery. In particular, there is aneed for an improved microcapsule-based technology for deliveringtherapeutic agents to diverse tissue types in a stable andtime-controlled manner.

Microcapsules have other uses in far ranging fields based on thechemical structure and properties of the microcapsules. For example, itmay be advantageous to use microcapsules and compositions comprisingsuch microcapsules with plastics, gels, pastes, adhesives, paintproducts, and generally with products that utilize polymers of any sort.Indeed, such improvements may lead to uses in industries unrelated tohealth and oral health such as in manufacturing, aeronautics, plasticmanufacturing, and similar fields.

One aspect of this invention addresses the challenge of incorporatingfillers into continuous phases. Compositions, methods and products thatbenefit from improved mechanical properties related to betterhomogenization of the continuous and discontinuous phase of a compositeis addressed in this invention. Another aspect of this invention relatesto further improvement of mechanical properties of a composite by theability to create novel fillers with unique morphologies and chemicalcompositions. This invention relates to the simplification of amanufacturing process that eliminates the need for additional steps forthe surface treatment of fillers. This invention not only improves themechanical properties of the composite, it does so in a way that thefiller can be made to carry therapeutic agents that can be released in acontrollable manner.

Composites are ubiquitous in structural materials. Typically a polymericcontinuous phase is mixed with discontinuous filler or fillers. Themixing of the filler into the continuous phase is done with the purposeof enhancing some property of the composite that could otherwise not beachieved by the continuous phase alone. A significant challenge thatremains in the development of composite materials is the discontinuitythat is created between the continuous phase and the filler. Thisdiscontinuity provides a pathway for crack propagation through thecomposite that results in mechanical properties that are not optimal,and at times prohibitive of using a particular continuous/fillercombination that would otherwise have been suitable for a targetapplication.

In order to address the mechanical issues created by the introduction ofthe filler into the continuous phase, additional manufacturing steps aretypically required. For example, in the field of dental materials, avariety of glass fillers are used to improve the performance of thecomposite. However, the glass fillers, if used untreated, provide afacile pathway for crack propagation in the material. In order toaddress this issue, glass fillers are subjected to an additionalmanufacturing step. Prior to inclusion into a dental formulation, theglass fillers are silanated. The silanation process provides a surfacetreatment that allows the glass filler to form a covalent bond to thecontinuous phase. The covalent linkage between the filler and thecontinuous phase eliminates the facile pathway for crack propagation. Inorder for the crack to propagate through the composite with the surfacetreated filler, significantly more energy is required, thereby enhancingthe fracture mechanics of the composite (e.g. fracture toughness isincreased).

Other examples of surface treatment exist to create a better bondingsurface in composites. One such example is corona, or plasma treatment.Many plastics, such as polyethylene and polypropylene, have chemicallyinert and nonporous surfaces with low surface tensions causing them tobe nonreceptive to bonding with printing inks, coatings, and adhesives.Although results are invisible to the naked eye, surface treatingmodifies surfaces to improve adhesion. However, due to the noncovalentnature of the surface treatment, plasma treatment typically becomes lesseffective over time.

The present application provides for improved or simplifiedmanufacturing methods of organic or hybrid based fillers used incomposite materials. The method of microcapsule synthesis eliminates theneed for additional manufacturing steps typically required for theeffective incorporation of discontinuous fillers into compositematerials. Many composite based products are envisioned from thisinvention, including composite based formulations of sealants, cements,glazes, varnishes and many other dental and nondental based materials.

Compositions, methods and products that benefit from improved mechanicalproperties related to better homogenization of the continuous anddiscontinuous phase of a composite. This is achieved by functionalizingthe exterior surface of microcapsules such that the microcapsules cancovalently bond with the continuous phase. Accordingly, the continuousphase and the discontinuous phase are covalently bonded upon initiationor reaction of the materials. This approach can generally beaccomplished by preparing microcapsules that have a polymeric shell.This polymeric shell can be synthesized with functional groups off thebackbone or side chain of the polymer that can subsequently undergochemical reactions with other functional groups present in the monomeror polymer of a continuous phase resulting in a bond between themicrocapsule and the continuous phase.

Accordingly, the present disclosure describes improvements inmicrocapsules, their formulation, and compositions, compounds, andmethods for the mineralization of various physiological tissues,including mineralized connective tissues, primarily of bone and teethusing such microcapsules. Mineralized connective tissue or tissuesinclude teeth, bone, and various connective tissues such as collagen,cartilage, tendons, ligaments and other dense connective tissue andreticular fibers (that contains type III collagen) of a mammal,including a human being. For purposes of definition in thisspecification, “mineralized tissue” shall mean bone and teethspecifically. Each of the terms “mineralization” and “tissuemineralization” are used interchangeably herein and mean a process inwhich crystals of calcium phosphate are produced by bone-forming cellsor tooth-forming cells and laid down in precise amounts within thefibrous matrix or scaffolding of the mineralized tissue as definedhereinabove.

Calcium phosphates are a class of minerals containing, but not limitedto, calcium ions together with orthophosphates, metaphosphates and/orpyrophosphates that may or may not contain hydrogen or hydroxide ions.

For purposes of definition in this specification, “remineralization” isthe process of restoring minerals, in the form of mineral ions, to thehydroxyapatite latticework structure of a tooth. As used herein, theterm “remineralization” includes mineralization, calcification,recalcification and fluoridation as well as other processes by whichvarious particular ions are mineralized to the tooth. The term “teeth”or “tooth” as used herein includes the dentin, enamel, pulp and cementumof a tooth within the oral cavity of an animal, including a human being.

In certain embodiments, the present invention provides methods forremineralization surface of a tooth material by using the microcapsulesformulations, as described herein, containing one or more materialsdisposed of therein which are suitable for being released from themicrocapsule for remineralizing a tooth material or bone surface. Forpurposes of definition in this specification, as referred to herein, a“tooth material” refers to natural teeth, dentures, dental plates,fillings, caps, crowns, bridges, dental implants, and the like, and anyother hard surfaced dental prosthesis either permanently or temporarilyfixed to a tooth within the oral cavity of an animal, including a humanbeing.

Another aspect of this invention relates to further improvement ofmechanical properties of a composite by the ability to create novelfillers with unique morphologies and chemical compositions. Accordingly,this invention relates to the simplification of a manufacturing processthat eliminates the need for additional steps for the surface treatmentof fillers. This invention not only improves the mechanical propertiesof the composite, it does so in a way that the filler can be made tocarry therapeutic agents that can be released in a controllable manner.

The present invention presents compositions and methods that improve themechanical properties of a composite or improve the manufacturingprocess of fillers used in composites. The present invention providesproducts that are useful in a number of industries, especially for oralhealth care. The present invention provides compositions that includefillers, especially liquid filled microcapsules that are surfacefunctionalized with a polymerizable functional group. These fillers,when combined with monomers and an initiator allow for the generation ofa composite that has the continuous and discontinuous phases covalentlybonded together. The covalent bonding of the continuous anddiscontinuous phases leads to a significant improvement in mechanicalproperties of a composite, especially in the area of fracture mechanics.

The composition of this invention affords for the opportunity ofproducing bondable bioactive microcapsules if the filler is amicrocapsule filled with a liquid that contains a therapeutic agent. Thecomposition of this invention not only provides superior fractureproperties by nature of the covalent bonding between the filler andcontinuous phase, but it can provide for improvement of other mechanicalproperties if the microcapsule is filled with energy absorbing materialssuch as rubbers or silicones. Indeed, several fillers can be utilized toproduce a variety of microcapsules, which can then be combined together.In particular embodiments it is particularly suitable to mix one of moreof a variety of microcapsules to provide a composition with certainphysical and chemical properties, whereby the release of differentmaterials from the different microcapsules provides advantageouseffects. Accordingly, antimicrobial, remineralizing, and physicalproperty enhancing microcapsules can be admixed alone, on incombinations thereof. Other suitable filler components includedetergents, dyes, abrasives, flavors, and other components known to oneof skill in the art that are suitable for filling in a microcapsule.

The bondable bioactive microcapsules are suitable for industrialproducts in the dental materials industry. If the liquid encapsulated inthe bondable microcapsule contained aqueous salt solutions of a calcium,phosphate or fluoride containing salt, then incorporation of thosemicrocapsules in a dental materials product for promotingremineralization would be desirable. If the liquid encapsulated in thebondable microcapsule contained aqueous solutions of an antimicrobialagent such as benzalkonium chloride or cetylpyridinium chloride, thenincorporation of those microcapsules into a dental materials productwith antimicrobial properties would be achieved.

In essence, this invention simultaneously enhances the mechanicalproperties and simplifies the manufacturing of a composite by virtue ofhaving built-in surface functionalization, while adding the benefit ofhaving the filler be therapeutic or mechanically toughening depending onits chemical composition.

This results in a composition comprising of a continuous phase and adiscontinuous phase, wherein in the continuous phase is provided amonomer and optionally an initiator, and the discontinuous phase amicrocapsule encapsulating a material, for example, an aqueous solutionof a salt, wherein said microcapsule has a surface functionalized with apolymerizable functional group capable of polymerizing with saidmonomer. Indeed, in particular embodiments, the salt is a calcium,fluoride, or phosphate salt, or combinations thereof. Other suitablesalts may be preferred in nondental treatments and are also suitable foruse with the functionalized microcapsules described herein.

Similarly, the composition can be described as comprising a polymericcontinuous phase, a microcapsule encapsulating a material, for example,an aqueous solution of a salt, specifically calcium, fluoride orphosphate or a combination thereof, wherein said microcapsule has asurface functionalized with a polymerizable functional group capable ofpolymerizing with said monomer.

Indeed, in particular embodiments, the composition comprises a polymericcontinuous phase, a microcapsule encapsulating a fluid, wherein saidmicrocapsule has a surface functionalized with a polymerizablefunctional group that is covalently bonded to the continuous phase.

A particularly suitable composition for pit and fissure sealant withremineralization capabilities and enhanced fracture toughness isdescribed as follows. A pit and fissure sealant containing resin, glassfillers, microcapsules with acrylate functionalized surfaces thatcontain a 5 M aqueous solution of calcium nitrate, microcapsules withacrylate functionalized surfaces that contain a 6 M aqueous solution ofpotassium phosphate dibasic, and microcapsules with acrylatefunctionalized surfaces that contain an aqueous solution of sodiumfluoride, and at least one photoinitiator.

Photoinitiators used in the compositions and materials described hereinare additives that assist in the formation of polymers from themonomers. In many dental composite materials the photoinitiator issoluble in the continuous phase. Activation of the photoinitiator isperformed by providing a light source, typically a high energy lightsource in the visible spectrum, which activates the initiator toinitiate the polymerization process. However, suitable photoinitiatorsmay also be in the discontinuous phase in the embodiments describedherein. Other initiators may also be suitable based on the circumstancesof use as is known to one of ordinary skill in the art.

In other compositions, a composition for pit and fissure sealant withantimicrobial properties and enhanced fracture toughness is described asfollows. A pit and fissure sealant containing resin, glass fillers,microcapsules with acrylate functionalized surfaces that contain a 5%w/w aqueous solution of benzalkonium chloride (5% w/w), andphotoinitiators (1 wt. %).

In other compositions, a composite material with enhanced mechanicalproperties is described as follows. A resin mixture (16 wt. % total) wasfirst made by combining UDMA resin with TEGDMA resin in a 4:1 ratio. Aphotosensitizer (camphoroquinone) was added at 0.7 wt. % of the totalcomposition. An accelerator (ethyl-4-dimethylaminobenzoate) was added at0.25 wt. % of the total composition. An inhibitor (4-methoxyphenol) wasadded at 0.05 wt. % of the total composition. The resin,photosensitizer, accelerator and inhibitor were combined in a flask andmixed at 50° C. Upon homogenization, the above resin blend was mixedwith the following fillers (84 wt. % total): silanated strontium glass71 wt. %, fumed silica 10 wt. %, microcapsules with acrylatefunctionalized surfaces that contain high molecular weight silicone oil3 wt. %. Such composition can be used in any number of fields asdescribed herein.

A method for the production of surface functionalized microcapsulefilled with encapsulated aqueous remineralizing agents is described. Anoligomeric urethane is synthesized by the reaction of a diol and adiisocyanate. The diisocyanate is used in a molar excess. After 1 hourof reaction between the diol and diisocyanate, oligomeric urethane isachieved. At this point 2-hydroxyethylmethacrylate is added to thesynthesis medium of the urethane in order to terminate a percentage ofthe chain ends with methacrylate functional groups. The methacrylatefunctionalized urethane is isolated and added to an oil phase thatcontains an emulsifying agent. This solution is mixed, and a surfactantfree, inverse emulsion is formed as an aqueous solution containingsodium fluoride salt is added. After half an hour, diol is added to thesurfactant free, inverse emulsion to effectively polymerize the urethaneoligomers and encapsulate the aqueous solution. The microcapsules areisolated by centrifugation. The microcapsules have surface methacrylatefunctional groups that readily polymerize with other methacrylatemonomers of a continuous phase.

In view of the polymers utilized, the microcapsules arenonbiodegradable, and thus materials contained therein are released fromthe microcapsules via diffusion. This provides a different profile thanbiodegradable polymers or other polymers that are intended to burst,releasing the entire contents of the capsule at once.

In certain embodiments, the surface of the microcapsule is effectivelyfunctionalized with a vinyl group to allow the vinyl groups tocovalently bond with the monomer in the continuous phase. Thepreparation of the vinyl group is performed through a three stepprocess.

Step 1: Preparation of Surface Functionalized Shell Material

Step 2: Preparation of Surface Functionalized Microcapsule

Mix surface functionalized shell material, emulsifying agent, oil phase.Agitate mixture, with or without heat. Add an aqueous phase or otherliquid phase (silicon). Perform an interfacial polymerization of theurethane in the surfactant free inverse emulsion. Isolate surfacefunctionalized microcapsules.

Step 3: Formulation of Surface Functionalized Microcapsule

Combine surface functionalized microcapsule with desired continuousphase monomers and initiator. The surface functional group should bepolymerizable with the monomer to create a covalent link between thefiller and continuous phase.

In a preferred embodiment, a microcapsule is formed using polyurethanethat has a fraction of the polyurethane methacrylate terminated. Thisforms a nonbiodegradable capsule that is semipermeable to therapeuticagents such as calcium ions, fluoride ions, phosphate ions, benzalkoniumcations or cetyl pyridinium cations which can diffuse through themicrocapsule membrane. Furthermore, through reaction of the methacrylateon the surface of the nonbiodegradable microcapsule can then react withmethacrylate in the continuous phase, which forms a carbon-carbon bond.The carbon-carbon covalent bond increases the fracture toughness of thecomposite material by bonding the microcapsule to the continuous phase,as depicted in FIGS. 5, 6, and 8B.

FIG. 1, provides a representative flowchart for preparation of a surfacefunctionalized shell material wherein the surface of such shell isfunctionalized to allow for covalent bonding between the microcapsuleand the continuous phase. As described in Step 1, a chemical processresults in vinyl terminated components functionalized to the shell ofthe microcapsule. Following in Step 2, the surface functionalized shellmaterials are combined with an emulsifying agent and an oil phase. Themixture is agitated with or without heat before an aqueous phase orother liquid phase, such as silicone, is added. An interfacialpolymerization of the urethane in a surfactant free inverse emulsion.The surface functionalized microcapsules can then be isolated asappropriate.

In Step 3, the functionalized microcapsules are combined with thedesired continuous phase monomers and initiators. The surface functionalgroups on the microcapsules are polymerizable with the monomer to createcovalent bonds between the filler and the continuous phase. Thisprovides that the functionalized microcapsules are then covalentlybonded to the continuous phase.

Many classes of polymers can be utilized in the scope of the inventionand the choice depends on the specific desired properties. Examplesinclude, but are not limited to nonbiodegradable iterations of thefollowing classes: acrylic polymers, alkyd resins, aminoplasts,coumarone-indene resins, epoxy resins, fluoropolymers, phenolic resins,polyacetals, polyacetylenes, polyacrylics, polyalkylenes,polyalkenylenes, polyalkynylenes, polyamic acids, polyamides,polyamines, polyanhydrides, polyarylenealkenylenes,polyarylenealkylenes, polyarylenes, polyazomethines, polybenzimidazoles,polybenzothiazoles, polybenzoxazinones, polybenzoxazoles, polybenzyls,polycarbodiimides, polycarbonates, polycarboranes, polycarbosilanes,polycyanurates, polydienes, polyester-polyurethanes, polyesters,polyetheretherketones, polyether-polyurethanes, polyethers,polyhydrazides, polyimidazoles, polyimides, polyimines,polyisocyanurates, polyketones, polyolefins, polyoxadiazoles,polyoxides, polyoxyalkylenes, polyoxyarylenes, polyoxymethylenes,polyoxyphenylenes, polyphenyls, polyphosphazenes, polypyrroles,polypyrrones, polyquinolines, polyquinoxalines, polysilanes,polysilazanes, polysiloxanes, polysilsesquioxanes, polysulfides,polysulfonamides, polysulfones, polythiazoles, polythioalkylenes,polythioarylenes, polythioethers, polythiomethylenes,polythiophenylenes, polyureas, polyurethanes, polyvinyl acetals,polyvinyl butyrals, polyvinyl formals. One skilled in the art willfurther appreciate that the selection of the specific type of polymerwill impact the composition and permeability characteristics of themicrocapsules of the invention and that certain polymers are moreapplicable to certain industrial applications as compared toapplications in the field or dentistry.

In addition to the various possible polymers suitable for microcapsuleformation, suitable polymerizable functional groups may also be used.Embodiments as disclosed herein utilize a bond between a functionalizedmicrocapsule and a monomer. In preferred embodiments, a covalent bond isutilized, however, those of skill in the art will recognize than anynumber of suitable bonding mechanisms may be appropriate based on thechemistries utilized.

In preferred embodiments, the number of functional groups extending froma single microcapsule is between about 1% and 33% of all positionspossible on the polyurethane microcapsule. However, further preferredembodiments include between about 0.1% and 99.9% of all possiblepositions, and preferably between about 1% and 50%, about 1% and 25%,about 1% and 10%, about 1% and 5%, and about 1% to about 3%.

The amount of functional groups can be modified as known to one ofordinary skill in the art, wherein the number of functional groupstherefore can modify the properties of the ultimate polymer materialformed through combination of the microcapsule and the monomers. Indental materials encapsulating calcium, fluoride, and phosphate,preferred amounts are between about 1% and 25%, and more preferablybetween about 1% and 5%.

Indeed, FIG. 2 provides a sample of a liquid filled microcapsule 10,having the liquid phase 11 in contact with the polymer shell, and thefunctional group 12 attached thereto.

FIG. 3 provides further detail that representative ions, in this caseNa⁺ 16 and F⁻ 15 are each present in the liquid phase within themicrocapsule. As is known to one of ordinary skill in the art, allanions (including fluoride) must have accompanying cations. The sodiumand fluoride here are depicted ionically to depict that they aredissolved in water. Thereafter, through diffusion, the ions can exit themicrocapsule, as depicted through lines 13 and 14.

The semipermeable nature of the nonbiodegradable polymer allows fordiffusion of the materials contained therein. Diffusion rates can bemodified based on several factors as known to one of ordinary skill inthe art. The variables that control the diffusion rate include but arenot limited to the initial concentration of the ions in solution in themicrocapsule, the chemical composition of the microcapsule, and the w/wloading of the microcapsules in the continuous phase.

FIG. 4 provides a depiction of a bondable microcapsule which is ahydroxyethylmethacrylate functionalized microcapsule 10, which ispositioned in a mixture of monomers, in this case, a first monomertriethylene glycol dimethacrylate 30 and a second monomer bisphenol Aglycerolate dimethacrylate 40. These components can then react to allowthe functional group on the microcapsule 10 to bond to the monomers 30or 40 as depicted in FIG. 5, which shows a number of “m” microcapsulesin the polymeric structure 50 dependent on how many repeat units arepresent.

Indeed, FIG. 5 is essentially a close-up of a microcapsule at themolecular level, whereas FIG. 6 provides an example of two microcapsules10 bonded (whereas 20 is a bond between the polymer 50 and themicrocapsule) within a polymer 50 at a macro level. In FIG. 5, R 22 andR′ 21 can be a hydrogen or any functional group. Furthermore, thepolymer 50 can include any number of n, m, and o repeating units.Indeed, in a composite material, once formed, the number ofmicrocapsules within the material is solely dependent on the density andconcentration of the microcapsules in the material. Ultimately, thesurface functionalized microcapsule can be combined with the desiredcontinuous phase monomers and initiator to react. The surface functionalgroup should be polymerizable with the monomer to create a covalent bondbetween the filler (microcapsule) and the continuous phase monomer.

FIG. 7 depicts two (2) possible chemical structures 80 and 82 of theshell materials end groups. In two of the potential structures, theshell material can have isocyanate functional groups capable of reactingwith HEMA 84. This results in three (3) potential shell materials withmethacrylate end groups 86, 88 and 90. One structure can have a hydroxylend group and a methacrylate end group, one structure can have anisocyanate end group and a methacrylate end group, and one structurecould have potentially two methacrylate end groups. Accordingly, thesemake a functionalized shell for the microcapsule 10 which can be bondedas depicted in FIG. 8.

FIG. 8 further depicts that the functionalized microcapsule 10 can thencombine with a monomer 30. A polyurethane terminated with at least onemethacrylate group 71 can react with a monomer such as triethyleneglycol dimethacrylate 30 during a polymerization. In this reaction, thecarbon-carbon pi bonds 72 add together in a series of addition reactionto generate a polymeric structure where the methacrylate group 71 isbonded to the monomer 30, thus binding the microcapsule 10 to themonomer. In FIG. 8 and as described herein, this can be accomplished bya radical reaction in which the methacrylate functional group of themicrocapsule adds to a growing polymer chain or network.

In other embodiments, a composition having functionalized microcapsulesis suitable for admixing into one of any known paint products. In theaspect of paint, adding functionalized microcapsules to the body ofpaint, provides additional strength and structure to the paint productand increase the strength of the paint. For example, such a paint mayfurther resist tearing or peeling as compared to currently availableproducts.

Similarly, in use in the plastic industry, functionalized microcapsulescan impart additional strength while maintaining elasticity orflexibility of a product. Alternatively, in other uses, additionalrigidity can be imparted, simply depending on the components within thefunctionalized microcapsules.

Certainly, such microcapsules can be further utilized in adhesiveproducts, wherein the properties of an adhesive can be manipulated basedon the component of a functionalized microcapsule such that the adhesivehas greater lateral or shear strength or has increased flexibility whilemaintaining a bond. Similarly, other characteristics can be envisionedbased on the component of the functionalized microcapsule.

Finally, it the use of such functionalized microcapsules can befacilitated into one of any number of polymer-based products. Thisallows for modification and improvement of any number of materials,including wearable fabrics, ballistic products, solid and rigidproducts, etc. However, by using the functionalized microcapsules, thecharacter of the polymer can be amended based on the need and ultimateuse of the product.

Accordingly, the compositions and materials that can be encapsulatedinto the various microcapsules are far ranging. These includerestorative ions, such as calcium, phosphate, and fluoride,antibacterial components such as benzalkonium or cetylpyridinium ions,but may also include other materials. Additional compositions mayinclude other suitable ionic materials, antibacterial materials,whitening materials, and the like. However, in other classes of use,such as in industrial uses, microcapsules may contain other materials toenhance the physical properties of the materials. For example, rubbermaterials, silicone materials, or other similar natural or syntheticmaterial or polymers that provide for different structural properties.Suitable silicone materials include, but are not limited to those havinga molecular weight between about 12,500 and 2,500,000 g/mol.

The use of an inhibitor may be suitable in certain embodiments as amaterial to prevent autopolymerization in the material.

Accelerator and photosensitizer are frequently used together inphotoinitiator chemistry to initiate the polymerization of the materialand to accelerate the polymerization. Therefore, the material can bepolymerized quickly in certain circumstances, such as when making adental composite in the mouth.

These components can therefore be imparted into solid, liquid, gels,aerosols and the like. By imparting predetermined characteristics to thefunctionalized microcapsules, it is possible to impart predeterminedfunctionality to such a product.

EXAMPLES Example 1 Composition of Matter Example 1a (Sealant A, 2 wt. %Bondable Microcapsule)

A composition for pit and fissure sealant with remineralizationcapabilities and enhanced fracture toughness is described as follows. Apit and fissure sealant containing resin (67 wt. %), glass fillers (30wt. %), microcapsules with acrylate functionalized surfaces that containa 5 M aqueous solution of calcium nitrate (2 wt. %), and photoinitiators(1 wt. %).

Composition of Matter Example 1b (Sealant B, 2 wt. % NonbondableMicrocapsule)

A composition for pit and fissure sealant with remineralizationcapabilities and enhanced fracture toughness is described as follows. Apit and fissure sealant containing resin (67 wt. %), glass fillers (30wt. %), microcapsules without acrylate functionalized surfaces thatcontain a 5 M aqueous solution of calcium nitrate (2 wt. %), andphotoinitiators (1 wt. %).

Composition of Matter Example 1c (Sealant C, 5 wt. % BondableMicrocapsule)

A composition for pit and fissure sealant with remineralizationcapabilities and enhanced fracture toughness is described as follows. Apit and fissure sealant containing resin (64 wt. %), glass fillers (30wt. %), microcapsules with acrylate functionalized surfaces that containa 5 M aqueous solution of calcium nitrate (5 wt. %), and photoinitiators(1 wt. %).

Composition of Matter Example 1d (Sealant D, 5 wt. % NonbondableMicrocapsule)

A composition for pit and fissure sealant with remineralizationcapabilities and enhanced fracture toughness is described as follows. Apit and fissure sealant containing resin (64 wt. %), glass fillers (30wt. %), microcapsules without acrylate functionalized surfaces thatcontain a 5 M aqueous solution of calcium nitrate (5 wt. %), andphotoinitiators (1 wt. %).

TABLE 1 The fracture toughness for the four (4) sealant formulationsthat contain nonbondable microcapsules as controls and the new bondablemicrocapsules. Sample Average Fracture Toughness, (K_(IC)) 2% w/wnonbondable microcapsules, 1.2 ± 0.2 control 2% w/w bondablemicrocapsules 2.0 ± 0.4 5% w/w nonbondable microcapsules, 1.3 ± 0.3control 5% w/w bondable microcapsules 2.0 ± 0.3

Accordingly, by addition of bondable microcapsules, the average fracturetoughness increases by more than 50% as compared to an equivalent weight% control with nonbondable microcapsules.

Composition of Matter Example 2 (A Plurality of Bondable MicrocapsulesContaining Different Therapeutic Agents in the Same Formulation)

A composition for pit and fissure sealant with remineralizationcapabilities and enhanced fracture toughness is described as follows. Apit and fissure sealant containing resin (64 wt. %), glass fillers (30wt. %), microcapsules with acrylate functionalized surfaces that containa 5 M aqueous solution of calcium nitrate (2 wt. %), microcapsules withacrylate functionalized surfaces that contain a 6 M aqueous solution ofpotassium phosphate dibasic (1 wt. %), microcapsules with acrylatefunctionalized surfaces that contain a 0.8 M aqueous solution of sodiumfluoride (2 wt. %), and photoinitiators (1 wt. %).

Composition of Matter Example 3

A composition for pit and fissure sealant with antimicrobial propertiesand enhanced fracture toughness is described as follows. A pit andfissure sealant containing resin (64 wt. %), glass fillers (30 wt. %),microcapsules with acrylate functionalized surfaces that contain a 5%w/w aqueous solution of benzalkonium chloride (5% w/w), andphotoinitiators (1 wt. %).

Composition of Matter Example 4

A composition for a dental resin composite with enhanced mechanicalproperties is described as follows. A resin mixture (16 wt. % total) wasfirst made by combining UDMA resin with TEGDMA resin in a 4:1 ratio. Aphotosensitizer (camphoroquinone) was added at 0.7 wt. % of the totalcomposition. An accelerator (ethyl-4-dimethylaminobenzoate) was added at0.25 wt. % of the total composition. The photosensitizer and acceleratorare commonly used together in photoinitiator chemistry. An inhibitor(4-methoxyphenol) was added at 0.05 wt. % of the total composition. Theresin, photosensitizer, accelerator and inhibitor were combined in aflask and mixed at 50° C. Upon homogenization, the above resin blend wasmixed with the following fillers (84 wt. % total): silanated strontiumglass 71 wt. %, fumed silica 10 wt. %, microcapsules with acrylatefunctionalized surfaces that contain high molecular weight silicone oil3 wt. %.

Example 5

A composition for a flexible denture base material with enhancedmechanical properties is described as follows. A resin mixture (16 wt. %total) was first made by combining UDMA resin with TEGDMA resin in a 4:1ratio. A photosensitizer (camphoroquinone) was added at 0.7 wt. % of thetotal composition. An accelerator (ethyl-4-dimethylaminobenzoate) wasadded at 0.25 wt. % of the total composition. An inhibitor(4-methoxyphenol) was added at 0.05 wt. % of the total composition. Theresin, photosensitizer, accelerator and inhibitor were combined in aflask and mixed at 50° C. Upon homogenization, the above resin blend wasmixed with the following fillers (30 wt. % total): silanated strontiumglass 22 wt. %, fumed silica 3 wt. %, microcapsules with acrylatefunctionalized surfaces that contain high molecular weight silicone oil5 wt. %.

Although the present invention has been described in considerabledetail, those skilled in the art will appreciate that numerous changesand modifications may be made to the embodiments and preferredembodiments of the invention and that such changes and modifications maybe made without departing from the spirit of the invention. It istherefore intended that the appended claims cover all equivalentvariations as fall within the scope of the invention.

What is claimed is:
 1. A composition comprising a monomer, an initiator,and a nonbiodegradable microcapsule encapsulating an aqueous solution ofa salt wherein said microcapsule has a surface functionalized with apolymerizable acrylate functional group capable of polymerizing withsaid monomer.
 2. The composition of claim 1 wherein the aqueous solutionof a salt contains ions selected from the group consisting of: fluoride,calcium, phosphate, and combinations thereof.
 3. The composition ofclaim 1 comprising a combination of salt ions wherein the combination ofsalt ions is achieved by using a plurality of microcapsules that containeither fluoride, calcium, or phosphate, wherein each microcapsulecontains only one of the fluoride, calcium, or phosphate ions.
 4. Thecomposition of claim 1 wherein the aqueous solution of a salt containsbenzalkonium or cetylpyridinium ions.
 5. The composition of claim 1wherein the aqueous solution of a salt is specifically a combination ofsalts that result in a buffered solution.
 6. The composition of claim 5wherein the buffered solution contains a therapeutic agent.
 7. Thecomposition of claim 1 further comprising a photoinitiator.
 8. Acomposition comprising a polymeric continuous phase and a discontinuousphase wherein the continuous phase comprises a polymeric material andthe discontinuous phase comprised a microcapsule encapsulating anaqueous solution, wherein said microcapsule has a surface functionalizedwith a polymerizable acrylate functional group and is bonded to thepolymeric continuous phase.
 9. The composition of claim 8 wherein theaqueous solution is an aqueous solution of a salt that contains ionsselected from the group consisting of: fluoride, calcium, phosphate, andcombinations thereof.
 10. The composition of claim 8 wherein the aqueoussolution is an aqueous buffered therapeutic solution comprisingbenzalkonium or cetylpyridinium ions or combinations thereof.
 11. Thecomposition of claim 8 comprising a plurality of microcapsules thatcontain either a fluoride, calcium, phosphate, benzalkonium,cetylpyridinium, or iodide ions wherein each microcapsule contains onlyone of the ions.
 12. The composition of claim 8 wherein said aqueoussolution comprises a silicone or rubber-based material.
 13. Thecomposition of claim 8 wherein said polymeric continuous phase comprisesat least one monomer and a photoinitiator in the continuous phase and amicrocapsule and an inhibitor in the discontinuous phase, and wherein alight source activates the photoinitiator which allows the monomers inthe continuous phase to polymerize and bind with the acrylate group onthe microcapsule.
 14. The composition of claim 13 wherein the at leastone monomer comprises TEGMA and bisGMA monomers.
 15. The composition ofclaim 13 wherein the microcapsule is between 2% and 5% w/w of thecomposition and wherein said acrylate functional group is a methacrylatefunctional group on the surface, and wherein the methacrylate group iscapable of reacting with a methacrylate group positioned on the TEGMAand bisGMA monomers in the continuous phase.
 16. A method formanufacturing a composition having a microcapsule and a continuous phasewherein said microcapsule comprises a functionalized surface capable ofcovalently bonding to the continuous phase comprising: mixing anoligomeric urethane by reaction of a diol and diisocyanate, in which thediisocyanate is used in molar excess, and reacting for a about 1 hour;adding 2-hydroxyethylmethacrylate to the resulting oligomeric urethanemixture to terminate chain ends with methacrylate functional groups;isolating the functionalized urethane; adding the isolatedfunctionalized urethane to an oil phase comprising an emulsifying agentand an organic solvent wherein a surfactant free inverse emulsion isformed with the addition of an aqueous phase that may contain a salt;adding diol to the surfactant free reverse emulsion to polymerize theurethane oligomers and encapsulate the aqueous solution; and isolatingthe microcapsules by centrifugation.
 17. The method of claim 16 whereinthe continuous phase comprises momomers selected from the groupconsisting of: TEGDMA, bisGMA, and combinations thereof.
 18. The methodof claim 16 wherein the aqueous phase comprises a fluoride, calcium,phosphate, benzalkonium, cetylpyridinium, iodide ions, or combinationsthereof.
 19. The method of claim 15 wherein the aqueous phase comprisesa silicone or rubber-based material.